This invention relates to chromatography columns and methods of operating them. In particular, it relates to structures and methods useful in moving column end units, such as in packing and/or in unpacking a particulate medium which in use occupies a bed space of the column. The invention relates to any size column, and particularly relates to larger columns of the kind useful in industrial preparative chromatography, whose internal diameters might typically be from 200 mm upwards, perhaps up to 3000 mm.
A conventional industrial-scale chromatography column consists of a column housing having a tubular side wall—almost always cylindrical—and opposed axially spaced end units (commonly referred to as plates, or end plates), which together with the side wall define an enclosed bed space to contain a bed of particulate medium in use. For most processes the particulate medium is closely packed to form a packed bed which does not move as the liquid containing components to be separated (the mobile phase) is passed through the column. However some columns/processes use a more loosely dispersed or fluidised/expanded particle bed for the chromatographic process.
The column end units have conduits for the passage of mobile phase liquid, combined with a permeable structure or element that retains the appropriate particulate medium in the bed space. Typically, the permeable structure or element is a permeable layer (e.g., a mesh or sinter) extending across the end of the column, that is permeable to liquid but not to the particulate medium. Packed bed columns usually have such a permeable layer at both ends of the column.
Typically, columns are axially vertical, i.e., with top and bottom end units, and the following assumes this for convenience of description.
Conventionally, at least one of the end units is axially slidable in sealing relationship with the tubular side wall, e.g., so that the bed space volume can be adjusted. Often the top end unit has a slidable plate and the bottom end unit has a fixed end plate. When forming packed columns, after filling the bed space with sufficient slurry to form a packed bed of the required depth, the slidable plate (sometimes referred to as a piston or end unit piston as explained below) is moved towards the fixed end plate until the bed is firmly captured between the two permeable end structures.
Recently, chromatography columns with end units including a slurry valve have become popular. In these columns it is not necessary to take off the top end unit to pour in slurry. The slurry can be pumped in directly through the valve, initially expelling all the air from the bed space (referred to as “priming” the column) and then accumulating medium until there is sufficient medium for the bed. The valve is then shut, and the top end unit lowered to compress the bed if necessary. If desired, liquid can next be flowed down through the bed, referred to as “flow packing,” and a clear supernatant is formed above the packed bed. This down flow can be maintained by closing the top valve as the top piston is forced down, so that the piston supplants the liquid pump. Chromatography then proceeds without needing to open the column. In some versions the spent bed can be disposed of after chromatography also through a valve in an end unit, by opening the valve and pumping in a carrier liquid to remove the bed gradually as a slurry through the open valve. Examples of these slurry valves are seen in WO 96/10451, GB 2258415 and U.S. Pat. No. 6,117,317, using various arrangements of controlled flow ports or conduits for slurry control and various mechanical movements in the valve to open and close the ports or conduits. Embodiments of the present invention are particularly useful with columns having a valve-controlled slurry flow port or conduit in one or both of the end units.
Controlling the sliding movement of a movable end plate is technically problematic, especially with large columns. The usual end unit has (or is) a large-diameter piston sealing outwardly against the tubular side wall, and must be kept accurately in a radial plane as it moves, especially when it is slid axially onto the bed in a packing process. To maintain stable perpendicularity to the axis, a conventional construction has a number of vertically-adjustable peripheral support pillars extending up around the column housing from the mounting in the bottom end unit or bottom end plate. A top annular support element called an “adjuster flange” is supported on the support pillars and extends radially inwardly to some extent overhanging the column interior. The sliding end unit is then suspended from the adjuster flange by an array of vertical support rods, long enough for the piston to be lowered as far into the tubular housing as is likely to be necessary. Some vertical rods are fixed and function as guides, running slidably through openings in the adjuster flange. Other rods are fixed to the adjuster flange, and are connected to drive mechanisms mounted on or at the column base and operable to move the top end unit up and down. The drive may be screw operated or hydraulic, automatic or manual.
Whichever is used, there can be serious difficulties in keeping the end unit exactly level, i.e., in achieving exactly the same movement in all of the peripheral drive rods. With hydraulic drives, special systems are available for equalising the force/position in each of the circumferentially-distributed units as appropriate. However, these are expensive and complicated. Furthermore, space around a chromatography column is at a premium. The mentioned fixed pillars and drive rods already cause obstruction around the column, to the extent that it can be difficult to access the column interior for maintenance operations, e.g., removal/insertion of replacement permeable layers. It is highly undesirable to add to the obstruction and complication with further drive control mechanisms.